New Orleans Sign Advertising Voodoo
What I learnt at the recent AACR annual meeting in New Orleans is that cancer immunotherapy studies are requiring industry to think differently about clinical trial design.
As we move into combination trials of novel/novel combinations, how do we efficiently work out not only that each drug is safe, but in what patients they are likely to be most effective?
Readers who listened to the recent Novel Targets Podcast, “Of Mice and Men” will hear about some of the challenges associated with mouse models and how decisions are made moving into the clinic.
What I learnt from the podcast (and I hope you did too) is that if you are doing an immunotherapy trial in patients, the type of mouse model can really matter when it comes to interpretation of the preclinical data.
In response to a subscriber request, today’s post is about some of the statistical challenges in designing combination immunotherapy trials. To many, statistics is like voodoo, so this post does not go into any maths!
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Dr Michel Sadelain at AACR 2016
Dr Michel Sadelain, Director of Cell Engineering at Memorial Sloan Kettering Cancer Center in New York is a pioneer in the field of adoptive cell therapy.
Without his contribution, it is unlikely CAR T cell therapy would be where it is today.
He’s also President of the American Society of Gene and Cell Therapy (ASGCT), whose annual meeting is currently underway in Washington DC from May 4 to 7 (Twitter #ASGCT16).
Recently at the annual meeting of the American Association for Cancer Research (AACR), Dr Sadelain gave an outstanding presentation on turbo-charged CAR T cells, and shared some of his ideas on how to move the field forward.
In New Orleans, he also kindly spoke to BSB, and discussed how he thinks cell therapy researchers may obtain the “holy grail” of getting CAR T cell therapies to work effectively in solid tumors.
Dr Sadelin is someone who wants to break the immunology rules!
Not surprisingly, Dr Sadelain is optimistic and doesn’t share the view expressed by Dr Steven Rosenberg on CAR T cell therapies being limited to mostly hematologic malignancies when we interviewed him a year ago at last year’s ASGCT meeting. There’s nothing like a friendly controversy to spice the field up!
If you haven’t already done so, do listen to Dr Rosenberg on Episode 5 of the Novel Targets Podcast (@TargetsPodcast).
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King Kamehameha Statue, Honolulu HI
Honolulu: we’re continuing our coverage of the 2016 BMT Tandem meeting with a thought leader interview about a novel cancer immunotherapy approach that we’re excited about.
The cancer cell therapy landscape is still vastly uncharted territory in many respects.
The first CD19 targeted CAR T cell therapies expected to reach the market in 2017 are unlikely to be best-in-class, which leaves the commercial door open for other approaches that may be better, cheaper or more accessible.
If you are in the CAR T cell therapy space, there are plenty of competitive threats on the horizon, and the novel approach discussed in this post is one of them!
We’d heard a little about it, but hadn’t explored the concept in any detail, so were delighted to talk with a leading expert at the BMT Tandem meeting in Honolulu.
Subscribers can login or you can purchase access to read more about a cell therapy that could offer the benefits of a CAR without the need for genetic modification.
Honolulu: Yesterday we learnt the sad news that Dr Holbrook Kohrt (pictured) had died.
He was a Stanford hematologist/oncologist and rising star in the cancer immunotherapy field. Our thoughts go out to his family and friends.
I had the privilege to interview him last May at the Immunology 2015 meeting in New Orleans. His voice lives on in Episode 6 of the Novel Targets Podcast. One area of Dr Kohrt’s research was in combination immunotherapies, and how we can optimize efficacy, while avoiding significant immune adverse events.
So are checkpoints playing with fire when given in combination?
That was one of the provocative questions to come out of a scientific session entitled, “Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a platform for Novel Immunotherapies” at the BMT Tandem meeting in Hawaii last weekend. The session, chaired by Miguel-Angel Perales (@DrMiguelPerales) from Memorial Sloan Kettering Cancer Center, was both informative and interesting.
All the presentations were excellent, but one by Philippe Armand from the Dana-Farber Cancer Institute in Boston, “Checkpoint Blockade in SCT, Data & Hope, Promise & Peril” stood out for me. Dr Armand discussed checkpoint data pre and post stem cell transplantation and offered a perspective I had not heard before.
One of the provocative questions it raised was could checkpoints be playing with fire in some patients? Dr Armand kindly spoke with BSB after his talk.
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Holbrook Kohrt MD PhD (pictured right) is a Stanford medical oncologist and clinical researcher who is leading the way in cancer immunotherapy combination strategies targeting CD137 (4-1BB).
He’s a speaker I greatly enjoy listening to at meetings. Earlier this year at The American Association of Immunologists (AAI) annual meeting (Immunology 2015) in New Orleans, he gave a noteworthy presentation on combination monoclonal antibody therapy.
The potential of a combination of an anti-CD137 monoclonal antibody such as urelumab plus an anti-CD20 such as rituximab, was one that he appeared to be particularly excited about.
Dr Kohrt kindly spoke with BSB and shared his thoughts on the potential of immune modulators, which instead of acting as inhibitors to “release the brake,” like checkpoint inhibitors, act as agonists to “step on the gas” and rev up the immune system. This is a concept that many Pharma companies are currently looking to explore for new drug development opportunities, for example:
Source: Roche Media Briefing at ESMO 2014 in Madrid
When it comes to combination strategies, the big unanswered questions are which ones will produce big gains in response rates and survival outcomes, and which ones will be duds?
After all, much like targeted therapies, not all targets will be relevant in all tumour types – it will depend on the underlying immune system.
In New Orleans, Dr Kohrt talked about the potential advantages and concerns around combination strategies and why he’s particularly interested in CD137 as a novel target for immunotherapy.
In-Memorium Holbrook Kohrt
It is with great sadness that we must report that Holbrook Kohrt is no longer with us. He died, aged 38, on February 24, 2016.
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